This invention relates to novel compounds, pharmaceutical compositions and methods of inhibiting the 5-lipoxygenase pathway of arachidonic acid metabolism in an animal in need thereof which comprises administering to such animal an effective, 5-lipoxygenase pathway inhibiting amount of a pyridyl and phenyl substituted pyrrolo[1,2-a]imidazole, or pyridyl and phenyl substituted imidazo[1,2-a]pyridine, or a pharmaceutically acceptable salt thereof.
Davidson et al., U.S. Pat. No. 4,507,481, issued Mar. 26, 1985, disclose compounds of the formula: ##STR1## wherein: X is O or S(O)n;
n is O, 1 or 2; PA1 R.sup.1 is H, lower alkyl, phenyl, benzyl or benzyl substituted with lower alkylamino, lower alkylamino, nitro, halo, hydroxy or lower alkoxy-; PA1 R.sub.2 is H or XR.sup.1 ; PA1 A is CH.sub.2 or CH.sub.2 CH.sub.3 ; PA1 R.sub.3 and R.sub.4 are independently selected from A, lower alkyl, aryl, aryl substituted with lower alkyl, amino, lower alkylamino, nitro, lower alkoxy, hydroxy or halogen; provided that at least one of R.sub.3 and R.sub.4 is aryl or substituted aryl; and PA1 R.sub.5 and R.sub.6 are each H or join to form a double bond at the 2,3-position. PA1 2) One of R or R.sup.1 is 2-pyridyl or 3-pyridyl and the other is selected from: PA1 R is 4-pyridyl and R.sup.1 is selected from: PA1 R.sup.1 is 4-pyridyl and R selected from: PA1 One of R.sup.1 or R is pyridyl or alkyl substituted pyridyl and the other is PA1 and R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are H, or one or two of R.sup.2, R.sup.3, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.9 are independently selected from H or C.sub.1-2 alkyl; and n is 0 or 1; PA1 R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are H, or one or two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are independently selected from H or C.sub.1-2 alkyl; PA1 R.sub.10 is C.sub.1-4 alkyl; PA1 and X.sup.1 is selected from PA1 R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9 are all H, or one or two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.9, are independently selected from H or C.sub.1-2 alkyl; PA1 one of Y.sup.1 or Y.sup.2 is independently selected from 4-[1,2-dihydro-2-(C.sub.1-4 -alkyl]pyridyl substituted with N-(C.sub.1-8 alkanoyl), N-(C.sub.1-8 alkoxycarbonyl), N-(benzoyl), N-(phenoxycarbonyl), N-(phenylacetyl), or N-(benzyloxycarbonyl); PA1 and the other is selected from PA1 R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are H, or one or two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are independently selected from H or C.sub.1-2 alkyl; PA1 X is selected from: PA1 provided that when n is 1, and R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are H, X is other than 2,4-dimethoxyphenyl or 4-aminophenyl; or a salt thereof. PA1 R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are all H, or one or two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9, are independently selected from H or C.sub.1-2 alkyl; PA1 X.sup.2 is 4-(1,4-dihydro)pyridyl substituted with N-(C.sub.1-8 alkanoyl), N-(C.sub.1-8 alkoxycarbonyl), N-(benzoyl), N-(phenoxycarbonyl), N-(phenylacetyl), or N-(benzyloxycarbonyl); PA1 X.sup.1 is selected from PA1 R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are H, or one or two of R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, and R.sup.9 are independently selected from H or C.sub.1-2 alkyl; PA1 X is selected from:
Davidson et al. also disclose that such compounds are immunostimulants or immunosuppresants based on (a) their inhibiting or stimulating activity in a chemotaxis assay which measures the ability of a drug substance to influence the movement of murine macrophages responding to complement; (b) their immunosuppressing or activating activity in the Kennedy plaque assay in which an animal's humoral immune system is depressed artificially with 6-mercaptopurine. Neither the chemotaxis assay nor the Kennedy plaque assay is of any known utility for detecting or suggesting compounds which are inhibitors of the 5-lipoxygenase pathway. Davidson et al. also disclose that such compounds have antiinflammatory activity as determined by the carrageenan-induced paw edema assay in rats. As stated above, such assay has no known utility in detecting or suggesting compounds which are inhibitors of the 5-lipoxygenase pathway. Davidson et al. also disclose that such compounds have antiviral activity in mice with hepatitis; but such activity is of no known utility in detecting or suggesting compounds which are inhibitors of the 5-lipoxygenase pathway.